CytoImmune Therapeutics

Cytoimmune is hosting, so many interesting projects on the island. This will be an opportunity to get together and discuss everything happening in biotech on the Island on a semi-regular basis. Welcome ideas for attendees and presentations.

We are seeking participants diagnosed with TBCK-related encephalopathy, a rare genetic disorder that affects the nervous system, causing developmental delays, intellectual disability, and muscle weakness. Also known as the "Boricua gene" due to its prevalence in Puerto Rican families, this condition is extremely rare, making every contribution crucial for advancing research and potential treatments. If you or someone you know has a confirmed TBCK gene mutation and would be willing to participate in this vital research, please reach out to me for more details. Key Details: Seeking individuals with confirmed TBCK gene mutations Samples will be used in cutting-edge genetic research Confidentiality will be strictly maintained Your contribution could be pivotal in advancing treatment options for those with TBCK-related disorders Please consider reposting to help us reach as many people as possible. Since TBCK-related disorder is so rare, every connection can make a difference! #RareDisease #TBCK #BoricuaGene #GeneticResearch #MedicalBreakthroughs #RepostForAwareness

Our TRACK-NK cells are designed to overcome one of the biggest challenges in cancer therapy. How do they do it? By secreting IL-15…let me explain. Believe it or not, our immune system is actually VERY good at finding and killing cancer cells. It might sound unbelievable considering the vast number of people that develop cancer, but it’s true. Well, this being the case, if a cancerous tumor has formed, it must mean that, somehow, the cells were able to avoid being detected and/or destroyed by the immune system – otherwise, the tumor wouldn’t exist… Unfortunately, since our immune system is so good at finding and killing cancer cells, if a tumor begins to form, this places an enormous amount of evolutionary pressure onto the growing tumor, driving the acquisition of highly immunosuppressive characteristics among the survivors. As a result, the vast majority of cancers end up being incredibly immunosuppressive. This is a huge problem when it comes to treatment because most (I would argue ALL) treatments rely very heavily on the activation of an anti-tumor immune response. Our TRACK-NK cells not only directly target cancer cells via their multitude expression of activating receptors, they also directly combat intratumoral immunosuppression by secreting high volumes of the immunostimulatory cytokine IL-15. IL-15 is a highly immunogenic cytokine that augments T and NK cell proliferation, inhibits the onset of exhaustion, and can even promote the acquisition of memory functions. So, by trafficking to the tumor and releasing IL-15, our TRACK-NK cells can work to completely reshape the microenvironment to favor an anti-tumor immune response. For more information on our various cell therapy platforms and ongoing clinical trials, check out our website at cytoimmune.com

We use umbilical cord blood to manufacture allogeneic cell therapies. Here’s why. One of the biggest hurdles to generating an effective, scalable, and safe allogeneic cell therapy is choosing the right source of donor-derived cells. At Cytoimmune, we fully appreciate this fact which is why we took great care when deciding our source of cells. After a thorough evaluation of the advantages and disadvantages of various sources, including peripheral blood and induced pluripotent stem cells (iPSCs), we ultimately selected umbilical cord blood. Why? There are really four main reasons: ? 1. Abundant Source: UCB is readily available and often considered medical waste after childbirth, making it a highly obtainable resource for medical treatments. 2. Lower HLA Matching Requirements: UCB may require less stringent HLA matching, making the cells less likely to be eliminated by the host’s immune system. This ultimately results in a more persistent cell therapy inside the patient. 3. Healthier Cells: UCB cells are relatively free of DNA damage and less differentiated (younger), making them "healthier" and potentially more effective for therapeutic use. 4. Enhanced Engraftment & Reduced GVHD Risk: Studies show that UCB-derived cells have inherent “immune privileged” properties, have a higher likelihood of successfully engrafting upon infusion and pose less risk of graft-versus-host disease (GVHD) making them a safer option than something like adult, peripheral blood-derived cells. We use UCB-derived NK cells to fuel our pipeline of allogeneic NK cell therapies for oncology and autoimmunity. Check out our website (cytoimmune.com) to learn more about our approach and cell therapy manufacturing capabilities.

Our NK cells are uniquely positioned to combat autoimmune diseases. Why? Autoimmune diseases are typically caused by the emergence of “autoreactive” (reactive against self) T and B cells that mistake a part of the body as “foreign” and mistakenly target it for destruction. Typical treatment options, chemotherapy or steroids, work by suppressing the entire immune system in a completely unbiased manner and are often associated with severe side effects, limited efficacy, and must be administered indefinitely. Recent studies have revealed the tremendous therapeutic potential of CAR-T cells to treat autoimmune diseases by eliminating CD19+ B cells. However, while these recent successes are promising there is a significant flaw at the core of CAR-T cell-based cell therapies that may severely limit their activity against autoimmunity. What is it? Most CAR-T cell therapies exclusively target B cells while completely ignoring autoreactive T cells. Also, it is inherently difficult to develop a T cell-based therapy that can target T cells because, well, if T cells are engineered to kill other T cells, they would all kill each other in the blood bag - a phenomenon known as “fratricide”. Our allogeneic natural killer (NK) cell platform, TRACK-NK, offers a solution to this problem. First, since they are NK cells, they have no issues targeting B and T cells. Second, TRACK-NK cells are unique in that, instead of engineering them to target some surface marker on T or B cells, we culture them to express high levels of PD-L1 on their surface. PD-L1 on TRACK-NK cells binds to PD-1 on hyperactive immune cells, simultaneously suppressing both autoreactive T and B cell activity, combatting the symptoms of the autoimmune disorder (see figure). This approach provides a much more comprehensive and straight-forward method of inhibiting autoreactive immune cells and may prove to be a significantly more efficacious treatment option in indications where T cell therapies are not therapeutically viable. Check out our website (cytoimmune.com) for more information about our robust pipeline of allogeneic NK cell therapies for oncology and autoimmunity as well as our umbilical cord blood-derived cell therapy manufacturing capabilities.

PD-L1 is immunosuppressive, right? Well, not entirely. There’s more to the story. When you think of PD-L1, you probably think of it being expressed by cancer cells or T regulatory cells in the tumor, where it suppresses cytotoxic T cell activity and promotes disease progression. Well, did you know that it is also expressed on activated natural killer (NK) cells within the tumor microenvironment? It’s true and this phenomenon – NK cells expressing PD-L1 – seems to be exclusive to cancer… Seems odd. But it gets even more strange… PD-L1 expression on NK cells seems to STIMULATE the NK cell itself, and many studies have consistently shown that PD-L1-expressing NK cells exhibit enhanced cytotoxicity against cancer cells in both preclinical models and patient tumors. At Cytoimmune, we take advantage of this characteristic by deliberately manufacturing our NK cells to express high levels of PD-L1, augmenting their anti-cancer activity. However, if administered on their own, these cells will naturally inhibit PD-1-expressing T cells in the tumor, promoting disease progression. So, to block this, we co-administer our NK cells with a PD-L1 antibody. But get this, when a PD-L1 antibody binds to PD-L1 on NK cells, it boosts the immunological activity of the NK cell even further. So, by administering a PD-L1 antibody, we can simultaneously block PD-L1-mediated immunosuppression AND enhance the anti-cancer activity of our NK cells. Learn more about our NK cell therapy platforms and ongoing clinical trials at cytoimmune.com

Our TRACK-NK cells are designed to overcome one of the biggest challenges in cancer therapy. How do they do it? By secreting IL-15…let me explain. Believe it or not, our immune system is actually VERY good at finding and killing cancer cells. It might sound unbelievable considering the vast number of people that develop cancer, but it’s true. Well, this being the case, if a cancerous tumor has formed, it must mean that, somehow, the cells were able to avoid being detected and/or destroyed by the immune system – otherwise, the tumor wouldn’t exist… Unfortunately, since our immune system is so good at finding and killing cancer cells, if a tumor begins to form, this places an enormous amount of evolutionary pressure onto the growing tumor, driving the acquisition of highly immunosuppressive characteristics among the survivors. As a result, the vast majority of cancers end up being incredibly immunosuppressive. This is a huge problem when it comes to treatment because most (I would argue ALL) treatments rely very heavily on the activation of an anti-tumor immune response. Our TRACK-NK cells not only directly target cancer cells via their multitude expression of activating receptors, they also directly combat intratumoral immunosuppression by secreting high volumes of the immunostimulatory cytokine IL-15. IL-15 is a highly immunogenic cytokine that augments T and NK cell proliferation, inhibits the onset of exhaustion, and can even promote the acquisition of memory functions. So, by trafficking to the tumor and releasing IL-15, our TRACK-NK cells can work to completely reshape the microenvironment to favor an anti-tumor immune response. For more information on our various cell therapy platforms and ongoing clinical trials, check out our website at cytoimmune.com

Our TRACK-NK cells aren't just for cancer therapy. They can also treat autoimmune diseases. Here’s how. In autoimmune conditions, autoreactive immune cells are constantly being exposed to stimuli that forces them into a state of chronic activation. This tends to cause the accumulation of high levels of PD-1 on their surface as a result. Normally, to maintain a healthy balance of immunological activity, PD-L1 on other cells throughout the body binds to PD-1 on active immune cells and suppresses immune cell activity. In autoimmunity (and some inflammatory conditions) this balance can become dysregulated, resulting in hyperactivity of PD-1-expressing immune cells and subsequent damage to healthy tissue. Our allogeneic NK cells, TRACK-NK, are manufactured to express high levels of PD-L1. So, they bind to PD-1 on activated immune cells, suppressing their activity and dampening the autoimmune reaction without significantly compromising overall immune function. The best part? The elevated PD-L1 expression on TRACK-NK cells is not the result of any genetic manipulation – our manufacturing process causes the cells to do this naturally. This allows for the quick and simple production of an effective cell-based platform to treat autoimmunity. Also, since our cells do not target a specific immune cell lineage marker (like CD19 to target B cells), they are able to hinder the activity of a wide array of active immune cells – even other PD-1-positive NK cells – without the risk of fratricide (cell therapy targeting the cell therapy). Learn more about our NK cell therapy platforms and ongoing clinical trials at cytoimmune.com

We combine our TRACK-NK cells with a PD-L1 antibody, and the reason might surprise you. When most people think of Natural killer (NK) cells synergizing with antibodies, they think of a mechanism involving “antibody-dependent cellular cytotoxicity” or ADCC. This is when an antibody binds to an antigen on a target cell, an NK cell binds to the antibody, and then the NK kills target. Our TRACK-NK cells can also do this, but they harbor an additional function… You see, we manufacture our TRACK-NK cells to express high levels of PD-L1. So, instead of just binding to PD-L1 on tumors cells – directing NK cells to target them – the PD-L1 antibodies can also bind directly to PD-L1 on TRACK-NK cells themselves. When PD-L1 antibodies bind to PD-L1 on NK cells, this significantly enhances their function and hinders the onset of exhaustion, all in a manner that is totally INDEPENDENT of ADCC. Why is this important? This is a crucial advancement because it means PD-L1-expressing NK cells can benefit from PD-L1 antibodies, and effectively target and kill cancer cells even in the hostile tumor microenvironment where ADCC is often compromised. It also enables the PD-L1 antibody to exert therapeutic effects in tumors with low (or no) PD-L1 expression. At Cytoimmune, we believe that this innovative approach to harnessing the power of NK cells, in combination with PD-L1 antibodies, represents a significant step forward in cancer treatment. For more details about our NK cell therapy platforms and ongoing clinical trials, shoot us an email [email protected]